Publications

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining <i>homeostasis</i>, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.

SUMMARY Inelastic modeling of entire reinforced concrete (RC) buildings under seismic excitation is a complex problem that influences directly the predicted seismic performance. Modeling assumptions and conventions adopted become more important in existing RC frame response predictions, due to these structures’ structural characteristics and non conforming detailing. The problem is investigated for a typical existing five-story RC frame which has been designed for moderate seismicity according to the past generation of Greek seismic codes. Different plane frame finite element models are formulated adopting state of the art as well as state of the practice analysis codes and finite element formulations. The seismic performance of each model is estimated, following both a conventional static pushover as well as nonlinear timehistory analyses under different levels of seismic intensity. The models range from the simple yet widely adopted in practice concentrated plasticity elements with axial-flexural strength interaction only, to the more complex distributed damage stiffness or flexibility-based fiber elements accounting or not for joint deformations. The results of the analyses are compared at the global and primarily the local damage prediction levels, to reveal substantial discrepancies and scatter in key performance Response Indices introduced in a Performance Based (re)Design approach by the model limitations, which are often ignored. It is concluded that, in addition to standardization of the criteria and procedures of evaluation, the analytical model for evaluating these Response Indices should also be well defined to avoid error and conflict.

The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.

To investigate possible gender- and age-associated changes of the hypothalamic-pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy young (3-month) and old (23-month) female 344/N Fischer rats at the basal state and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At baseline, there were no major differences on HPT axis functions between young female and male animals. Old age was associated with impaired central thyroid function in both genders, albeit to a much lesser extent in females than in males. Plasma prolactin (PRL) levels were similar in young females and males but were higher in old females than males. IMMO inhibited HPT axis functions in both genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA levels were decreased by IMMO in young, but not in old rats of both genders. IMMO increased plasma PRL in young and old males, but did not have any effect in young and old females. In summary, these data indicate that age and gender exert diverse effects on HPT axis functions at baseline and after stress.

Social appearance anxiety is a type of social anxiety that is associated with body image perception and exacerbated by the use of social media, leading to feelings of loneliness. The purpose of this cross-sectional study was to examine the relations between social appearance anxiety, use of social media, and feelings of loneliness in Greek adolescents and young adults. The sample of the research consisted of 632 participants, 439 women (69.5%) and 193 men (30.5%), aged 18-35 years. The Social Appearance Anxiety Scale (SAAS), the Social Media Disorder Scale (SMDS), and the UCLA Loneliness Scale were the instruments used. Data collection was performed online, via Google forms. Multiple regression analyses were performed and demonstrated a significant positive correlation between the Social Appearance Anxiety Scale and the UCLA Loneliness Scale scores. The feeling of loneliness was predicted by the social appearance anxiety score (p < 0.0001). On the other hand, there was a significant negative correlation between the Social Appearance Anxiety Scale and the Social Media Disorder Scale scores (p = 0.002), suggesting that social media use may exacerbate appearance anxiety and, hence, loneliness. The findings suggest that there may be a complex, vicious reverberatory cycle between appearance anxiety, use of social media, and feelings of loneliness in some young people.

During the last decade research is gradually repositioning the antimalarial drug chloroquine, and certain related quinoline derivatives, as anticancer agents. Chloroquine and hydroxychloroquine, in particular, have relatively well-characterized toxicity profiles due to several decades of use for treatment of malaria. Previously published review articles provide an excellent overview of the diversity of chloroquine effects on cancer cells, both in the cell culture as well as on human tumors grafted into mice; and an account of the increasing pace of incorporation of hydroxychloroquine in combination treatment schemes for clinical studies. In this review we present some features that are common between cancers that are sensitive to quinoline derivatives, in particular features that are amenable to pharmaceutical intervention.

The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteronism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system.

We examined the presence and potential role of local corticotropin-releasing hormone (CRH) in experimental uveitis in rodents. This 41-amino acid peptide, originally isolated from the hypothalamus, is also secreted locally in experimentally induced and natural inflammatory sites, where it exerts autocrine or paracrine proinflammatory effects. Female Lewis rats were immunized with the major pathogenic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein in complete Freund's adjuvant, monitored daily, and killed 8, 9, 10, 12, 14, or 18 days later, after having developed uveoretinitis. Immunoreactive CRH (IrCRH) was detected by immunohistochemistry in the uveitic eyes in the cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid depending on the stage of the disease. The intensity of the IrCRH staining was positively correlated with the severity of the disease based on morphological criteria. The amount of IrCRH measured by RIA varied between 0.18 +/- 0.03 (mean +/- SE) and 0.79 +/- 0.07 pmol/g wet tissue (8th and 14th day of the disease, respectively). Ophthalmic IrCRH in uveitic rat eyes had similar chromatographic mobility as rat/human CRH-(1-41) by HPLC. Furthermore, female B10.A mice were immunized with interphotoreceptor retinoid-binding protein and treated during the induction (0-7 days) or expression (8-16 days) stages of the disease with ip injections of the anti-CRH antibody TS-2 or placebo nonimmune rabbit serum. The early anti-CRH treatment significantly decreased the disease intensity compared to that in placebo- or late-treated animals (P < 0.05, by analysis of variance). We conclude that IrCRH is present at the site of inflammation in rodent experimental uveitis and that its expression correlates with the natural history and intensity of the disease. Immune CRH appears to play an early pathogenetic role in the induction of experimental uveitis.

Validation of the Greek version of Mini Tinnitus Questionnaire (Mini-TQ-GR) as a Brief Screening Test for Assessment of Tinnitus-related Distress.Questionnaire study.401 General Military Hospital of Athens/Department of Audiology - Neurootology, Athens, Greece.Three hundred and one participants have anonymously completed the Mini-TQ-GR, comparing it to the Perceived Stress Scale (PSS 14) and Multidimensional Health Locus of Control Scale (MΗLoC) from November 2013 until May 2014.Mini-TQ-GR, compared to PSS 14 and MΗLoC.Factor analysis, has shown that the Mini-TQ-GR includes three main factors (Distress, Health pre-occupation and Depression), which explains the 59.05% of the total variance. The Cronbach alpha index was 0.865 approaching the respective reliability factor of the original validation (0.9). The test-retest correlation (intraclass correlation coefficient) was 0.9 (P < 0.01), close to the results of the original study (0.89). We found a positive correlation between tinnitus and perceived stress (r = 0.349**) and negative correlation between tinnitus and external locus of control (r = -0.124*, r = -0.198**) (chance, others).This study demonstrated that the Mini-TQ-GR has good internal consistency and reliability becoming a useful, validated measurement tool for tinnitus-induced distress.